Human monocyte-mediated antibody dependent cytotoxicity (ADCC) to K-562 cells has been examined using 51Cr-release assays and electron microscopy. Non-activated monocytes lysed antibody-coated K-562 cells rapidly, the observed lysis reaching a constant level of 28% after 6 h of co-culture. Lymphokine-activated monocytes mediated ADCC with a similar time course but with higher cytolysis level (42%) compared to non-activated monocytes. The cytolysis was dependent on the amount of antibody on the K-562 cells and on the number of effector cells present in the assay. Scanning electron microscopy revealed that sensitized target cells in contact with monocytes lost their microvilli. Lysis was probably extracellular, but a small number of completely engulfed intact target cells were observed. Lymphokine-activation of the monocytes led to a dissociation of the phagocytic and cytotoxic activity, indicating that phagocytosis is not directly involved in ADCC. Thin section- and freeze-fracture electron microscopy of the contact area between effector and target cells revealed no membrane specializations. The cells were always separated by a gap of 20-30 nm interrupted by characteristic invaginations in the opposing plasma membranes.